Charlotte Lewden

Changes in Cancer Mortality among HIV-Infected Patients: The Mortalité 2005 Survey

BACKGROUNDnThe goal of the current study was to describe the distribution and characteristics of malignancy related deaths among human immunodeficiency virus (HIV)-infected patients with use of data obtained from a national survey conducted in France in 2005 and to compare with results obtained from a similar survey conducted in 2000.nnnMETHODnThe underlying cause of death was documented using a standardized questionnaire fulfilled in French hospital wards and networks that were involved in the treatment of HIV-infected patients.nnnRESULTSnAmong the 1042 deaths reported in 2005 (964 were reported in 2000), 344 were cancer related (34%), which represented a significant increase from 2000 (29% of deaths were cancer related) (P=.02); 134 of the cancer-related deaths were AIDS related and 210 were not AIDS related. Among the cancer-related causes of death, the proportion of hepatitis-related cancers (6% in 2000 vs. 11% in 2005) and non-AIDS/hepatitis-related cancers (38% in 2000 vs 50% in 2005) significantly increased from 2000 to 2005 (P=.03 and P=.01, respectively), compared with the proportion of cancer that was AIDS related and adjusting for age and sex. Among cases involving AIDS, the proportion of non-Hodgkin lymphoma-associated deaths did not change statistically significantly between 2000 and 2005 (11% and 10% of deaths, respectively).nnnCONCLUSIONSnIn this study, an increasing proportion of lethal non-AIDS-related cancers was demonstrated from 2000 to 2005; meanwhile, the proportion of lethal AIDS-related cancers remained stable among HIV-infected patients. Thus, cancer prophylaxis, early diagnosis, and improved management should be included in the routine long-term follow-up of HIV-infected patients.

Emerging role of hepatocellular carcinoma among liver-related causes of deaths in HIV-infected patients: The French national Mortalité 2005 study.

BACKGROUND/AIMSnLonger exposure to hepatitis C (HCV) or B virus (HBV) and the increased use of hepatitis treatment might have an impact on liver-related deaths in patients co-infected with the Human Immunodeficiency Virus (HIV). We describe the proportion of liver-related deaths among HIV-infected patients in 2005 compared with 2000.nnnMETHODSnIn a nationwide survey (341 hospital departments involved in HIV management), all deaths of HIV-infected patients were prospectively reported. Deaths from either cirrhosis, hepatocellular carcinoma or fulminant hepatitis were defined as liver-related deaths.nnnRESULTSnOf the 898 deaths reported in 2005, liver-related causes accounted for 15.4%; this is compared to 13.4% in 2000. Among liver-related deaths, hepatocellular carcinoma increased from 15% to 25% (p=0.04). Among hepatocellular carcinoma-related deaths: in 2000, 10% were HCV-infected; in 2005, 25% were HCV-infected (p=0.03). Half of the HCV-related deaths had been treated for HCV but 98% remained HCV-RNA positive at time of death. The proportion of HBV-related deaths remained stable between 2000 and 2005.nnnCONCLUSIONSnLiver-related deaths, mainly liver cancers, have increased in HIV-infected patients in France despite wide access to HCV treatment. The stability of HBV-related deaths might be explained by the use of dually active antiretroviral drugs in co-infected patients.

Liver-related deaths in HIV-infected patients between 1995 and 2005 in the French GERMIVIC Joint Study Group Network (Mortavic 2005 Study in collaboration with the Mortalité 2005 survey, ANRS EN19).

More than 10 years after the introduction of combination antiretroviral therapy (cART), we examined the trend in the proportion of deaths caused by end‐stage liver disease (ESLD) in HIV‐infected adults in France between 1995 and 2005.

All-cause and liver-related mortality in HIV positive subjects compared to the general population: Differences by HCV co-infection

BACKGROUND & AIMSnWe aimed at comparing overall and liver-related mortality rates, observed in HIV positive subjects followed-up in the Cohorts of Spanish Network on HIV/AIDS Research stratified by HCV co-infection status, with the expected mortality of the general population of same age and sex in Spain, for the period 1997 - 2008.nnnMETHODSnWe estimated standardized mortality ratio (SMR) and excess mortality, comparing death rates from our cohort (globally and by HCV co-infection) with death rates from the general population standardized by sex in 5 year-age bands.nnnRESULTSnOverall, 5914 HIV positive subjects were included, 37.3% of which were co-infected with HCV; 231 deaths occurred, 10.4% of which were liver-related. SMR for all causes mortality for the HIV positive subjects was 5.6 (CI 95% 4.9-6.4), 2.4 (1.9-3.1) for HCV negative subjects and 11.5 (9.9-13.4) for HCV positive ones. Having HCV co-infection and AIDS yielded an SMR of 20.8 (16.5-26.1) and having AIDS and being HCV negative had an SMR of 4.8 (3.5-6.7). SMR for liver-related mortality was 1.8 (0.6-5.7) for HCV negative subjects vs. 22.4 (14.6-34.3) for HCV positive ones. Overall, both mortality rates as SMR and excess mortality rates were higher for injecting drug users (IDUs) than men having sex with men (MSM) and heterosexuals, patients with AIDS, with and without cART and for subjects included between 1997 and 2003.nnnCONCLUSIONSnThere was an excess of all-cause and liver-related mortality in our cohorts compared with the general population. Furthermore, HCV co-infection in HIV positive patients increased the risk of death for both all causes and liver-related causes.

Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France

The objective of the study was to describe the underlying causes of death of HIV-infected patients in the HAART era and to focus on those related to opportunistic infection (OI), in a national multicentre study (‘Mortalité 2000’). A total of 964 deaths were recorded and 924 cases were available for analysis. Underlying cause of death were AIDS-related (47%), viral hepatitis (11%), non-AIDS cancers (11%), cardiovascular diseases (7%) and others (11%). Among patients who died of AIDS events, 262 (27%) died of at least one OI. OIs reported at the time of death were Cytomegalovirus infection 67 times, Pneumocystis jiroveci pneumonia 56, disseminated Mycobacterium avium intracellulare infection 53 and cerebral toxoplasmosis 48. Compared to patients who died of other causes, patients who died of OIs were younger and more likely to be infected through heterosexual contact, in poor socioeconomic conditions, migrants, more recently diagnosed for HIV infection, and naive of antiretroviral therapy and OI prophylaxis. OIs are still a major cause of death in HIV-infected patient in the HAART era, especially among patients recently diagnosed for HIV infection and who do not have access to care, as well as in long term infected patients where prophylaxis should be revisited.

Factors Associated with Mortality in Human Immunodeficiency Virus Type 1–Infected Adults Initiating Protease Inhibitor–Containing Therapy: Role of Education Level and of Early Transaminase Level Elevation (APROCO–ANRS EP11 Study)

This study attempted to identify factors associated with mortality among human immunodeficiency virus (HIV)-infected adults starting a protease inhibitor (PI)-containing therapy. Among 1155 patients consecutively enrolled in the APROCO study between May 1997 and June 1998, clinical characteristics were as follows: median age, 36 years; median baseline CD4 cell count, 288 cells/mm(3); and median baseline plasma HIV RNA load, 4.4 log(10) copies/mL. After a median follow-up of 27 months, 48 deaths had occurred, of which 44% were related to acquired immune deficiency syndrome. The mortality rate was 2.9% at 12 months. When both data at baseline and data at 4 months after the start of PI therapy were considered, factors independently associated with mortality were (Cox model) low baseline plasma creatinine level, low school education level, low CD4 cell count at 4 months, low hemoglobin level, and elevated hepatic transaminase levels. Thus, social context plus clinical and biologic data, including the 4-month response to treatment, must be considered in treatment of HIV-infected patients.

Number of deaths among HIV-infected adults in France in 2000, three-source capture-recapture estimation

We estimated the number of deaths in France for the year 2000 in HIV-infected adults using three sources. The sources were (1) the Mortalité 2000 survey (M2000): 964 deaths were documented by 185 hospital wards involved in HIV management; (2) 1288 death certificates with a mention of HIV infection (INSERM-CepiDc) and (3) the French hospital database on HIV infection (FHDH) identified 654 deaths. The capture-recapture method was used with log-linear modelling. Overall 1559 deaths were observed. Estimation of the number of deaths in France was 1699 (95% CI 1671-1727). The completeness of M2000, CepiDc and FHDH were 55%, 76% and 38% respectively. Diversification of diseases and of causes of death in HIV-infected adults may explain: (1) the diversification of physicians involved in their management and incomplete coverage of M2000 and FHDH, and (2) why HIV infection was not mentioned in all death certificates.

Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in Sub-Saharan Africa

Introduction It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. Methods We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. Results Of 1,959 (913 non-Africans, 302 Europeans - African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15–29 year old woman was 607 (588–627) (non-African European), 469 (442–497) (European - African origin) and 570 (551–589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228–289), 155 (110–200), and 199 (174–224) cells/µL (p<0.01). Discussion Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.

Characteristics and response to antiretroviral therapy of HIV-1-infected patients born in Africa and living in France.

The world‐wide AIDS epidemic is reflected in Western Europe in an increasing number of HIV‐infected persons who originate from Africa. We describe the characteristics and response to antiretroviral therapy (ART) of HIV‐infected patients born in Africa and living in France.

Predictors of CD4+ T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

BACKGROUNDnLow CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure.nnnMETHODSnWe included individuals from the COHERE database who started antiretroviral therapy from 1998 onward and who experienced triple-class virological failure. CD4(+) T-cell counts obtained after triple-class virologic failure were analyzed using generalized estimating equations.nnnRESULTSnThe analyses included 2424 individuals with a total of 23 922 CD4(+) T-cell count measurements. In adjusted models (excluding current viral load and year), CD4(+) T-cell counts were higher with regimens that included boosted protease inhibitors (increase, 22 cells/µL [95% confidence interval {CI}, 3.9-41]; P = .017) or drugs from the new classes (increase, 39 cells/µL [95% CI, 15-62]; P = .001), compared with nonnucleoside reverse-transcriptase inhibitor-based regimens. These associations disappeared when current viral load and/or calendar year were included. Compared with viral levels of <2.5 log(10) copies/mL, levels of 2.5-3.5, 3.5-4.5, 4.5-5.5, and >5.5 log(10) copies/mL were associated with CD4(+) T-cell count decreases of 51, 84, 137, and 186 cells/µL, respectively (P < .001).nnnCONCLUSIONSnThe approximately linear inverse relationship between log(10) viral load and CD4(+) T-cell count indicates that there are likely immunologic benefits from lowering viral load even by modest amounts that do not lead to undetectable viral loads. This is important for patients with low CD4(+) T-cell counts and few drug options.